Chronic insomnia is among the most common symptoms during a major depressive episode (MDE), and the symptom of insomnia independently predicts poor quality of life (QOL), increased risk of suicide, and increased risk for recurrence of MDE. In contrast, preliminary evidence suggests that treatment of insomnia during MDE reduces the daytime symptom burden and improves QOL. Hypnotic medications (sleeping pills) are prescribed more commonly for psychiatric problems than for any other disorder, and this is not surprising since many of the newest antidepressants have little or no intrinsic sleep-inducing effect and may require that a hypnotic be prescribed along with the antidepressant. However, little is known about the efficacy and safety of combining the most commonly used antidepressant and hypnotic medications. This exploratory/development grant (R34 mechanism) will operationalize treatment of insomnia associated with MDE, will support the development of data-gathering methods for the proposed outcomes of interest, and shall test the feasibility of recruiting and retaining participants, and shall provide estimates of effect sizes for adding a hypnotic medication to an antidepressant in depressed patients with insomnia. Specifically, patients with MDE and insomnia who do respond to open fluoxetine monotherapy for 2 weeks are randomized to either placebo or the hypnotic zolpidem for 4 weeks, while continuing open fluoxetine. Participants shall be followed for an additional 4 months of naturalistic follow up after hypnotic/placebo therapy. Important outcome measures shall include reported and PSG sleep, mood, suicidal thinking, and QOL. We hypothesize that combined zolpidem and fluoxetine shall be associated with better QOL than receipt of fluoxetine and placebo. The projected effect sizes suggest that it is likely that statistically significant differences shall be found between groups that can be recruited during this exploratory/development grant. The application shall result in a proven methodology for examining the utility of hypnotic medications in depressed person with insomnia, and shall result in realistic sample size projections for a subsequent R01application that may include a three-armed comparison of placebo, versus hypnotic, versus sedating anti-depressant as add-on therapy for depression with insomnia.